The biological importance of the BOG and HMGB1 interaction is currently been pursued in both in vitro and in vivo (ulitizing the BOG -/- mouse model). We have also generated three transgenic lines expressing BOG at different levels and these mice are currently under investigation. Systematic analysis of the animals show consistent abnormalities in BOG transgenic mice as compared to wild-type mice. Among the most significant observations are an early atrophy of the pancreas, consisting of increased incidence of acinar cell apoptosis, increased inter-acinar space with inflammatory infiltrate, loss of acinar architecture and focal proliferation of epithelial-like cells in areas showing apoptotic cells and disorganized acinar architecture. Studies are ongoing aimed at explaining the BOG-induced alterations in pancreas. Histological examinations revealed an increase in cell turnover in the liver of transgenic animals. We are taking two experimental approaches to examine the biological consequences of this observation. The first one is DEN-induced tumorigenesis by i.p. injection of the carcinogen to 15 days animals, and the second one is liver regeneration after 2/3 partial hepatectomy. Both experiments are in progress. Also, we have shown that challenging the kidneys (high BOG expression) in BOG transgenic mice by administration of folic acid (i.p.) following standard procedure results in different kinetics for the injury-reparative response. The results indicate both an acceleration as well as amplification of renal injury based on histological analysis, kidney weight ratio and measurement of blood urea nitrogen. Further studies are necessary to provide molecular mechanisms mediating these differences. These challenging experiments for liver and kidney are being conducted in BOG knock-out animals as well.